Monday, August 19, 2013

Performing a Clean Zone Smoke Test

•
Direct compounding area (DCA): a critical area within the ISO Class 5—a
primary engineering control (PEC) where critical sites are exposed to
unidirectional HEPA-filtered air, also known as first air.• First air: the air exiting the HEPA filter in a unidirectional air stream that is essentially particle-free.•
Critical site: a location that includes any component or fluid pathway
surfaces (e.g., vial septa, injection ports, beakers) or openings (e.g.,
opened ampoules, needle hubs) exposed and at risk or direct contact
with air (e.g., ambient room or HEPA filtered), moisture (e.g., oral and
mucosal secretions), or touch contamination. Risk of microbial
particulate contamination of the critical site increases with the size
of the openings and exposure time.

To
test a clean zone, there are several issues like smoke reflux, dead
spots, and numerous smoke deviations to look for. It is important not to
separate the media filter from the wall since the farther it is from
the wall, the more reflux can be found. The HEPA filter media should be
flush with the walls of the clean zone and the front shield. The lexan
shield must be consistent in its area of opening from the HEPA filter
through the entire travel of the ISO-5 zone. Providing an incline to
expand the area of the opening will lower the velocities and uniformity
of the supply velocity. The uniformity of airflow velocity can be
affected by the type of filter utilized, like a room side replaceable
HEPA or ULPA filter. The typical loss of filter area also lowers the cfm
(cubic feet per minute) of the filter, thus lowering the velocities as
well as the volume.

To
perform this test personally, I have taken 10 measurements (two
columns, five rows) of velocity (testing a 2 by 4 ft. HEPA filter) using
a termo-anemometer held by a suitable stand to avoid the manual
fluctuations.

The
test procedure to validate these clean zones requires a
thermo-anemometer with a ring stand placing the probe of the anemometer
12 in. under the filter and beginning 6 in. away from the corner in each
direction. Then a 12 in. grid is set up with readings taken every 12
in. on center.

Most compounding
pharmacy clean zones have I.V. bars and bags which makes it important to
get the relative standard deviation as low as possible.
IEST-RP-CC-002.3 Section 6.1.1 states, "The maximum relative standard
deviation is typically 15% when using an electronic micro-manometer with
multipoint probe."

It's preferable to
keep the RSD below 10% to create the effect necessary to pass the smoke
challenge without high reflux, dead spots, or airflow that travels
sideways as opposed to straight down.

Selecting the filters for the clean zonesCareful
consideration of filter manufacturers is recommended as we have seen
large discrepancies in uniformity of face velocities among different
manufacturers and even filter types, like HEPA to ULPA designs.
Uniformity or unidirectional flow is the key to the functionality of
these systems as well as a continuous low level return beneath the work
zone.

Achieving a deviation of less than 14 degrees in an ISO-5 clean zoneThere
must be a continuous length of HEPA filter across a wall away from the
door with a 4 in. continuous wall return cavity along the back of the
area. The clean zone must have 100% coverage of the area, and use a
polycarbonate directional flow shield from the ceiling grid to 5 ft. off
the floor. The work table or zone should be moved nearer or farther
away from the back wall as necessary to cause a waterfall effect on the
front and back edges of the work table. A solid table produces an effect
similar to a biological safety cabinet centerline smoke split. (Note:
Perforated tables are difficult to clean and maintain.) Be sure the
table is no more than 30 in. in height and 30 in. or less in width. Once
the desired water fall effect is noticed, secure the work table at that
location and perform the smoke pattern test.

Performing the clean zone smoke pattern testPurpose: This
test determines that the airflow within the clean zone conforms to the
manufacturer's design criteria. This shows the airflow within the DCA
moving in a downward direction with no dead spots or refluxing in the
critical site. Be sure that the ambient air does not enter the clean
zone or other areas except through the supply HEPA filter. Once the air
enters the DCA, it must move to the returns without reentry. (Note: This
test should be performed following completion of the airflow velocity,
volume, room air changes per hour, room pressures, and uniformity
tests.)

Good results can be
achieved using a theatrical fog generator that has a mixture of glycol
with a fan speed controller connected to a delivery tube, supported by a
hands-free stand (1 in. diameter PVC with small holes to create a
laminar-like curtain smoke pattern). It is recommended that the PVC tube
be the same size as the distance between the front shield and the wall.• Adjustable support stand• Plumb bob• Tape measure• Video or digital camera

Procedure: • Place the delivery tube with the plumb bob.• Turn on the smoke generator and adjust the fan speedcontrol to get the desire laminar airflow.• Introduce the aerosol stream isokinetically and, as nearly as practical, isothermally.• Generate the smoke remotely from the vicinity of the source.•
Move the smoke tube through the entire area to be tested, sliding the
hands-free stand slowly so that the whole clean zone area is observed
and video recorded.• With the pointer mounted in the support stand,
at the work table exit plane, measure the offset distance (Δs) between
the theoretical straight-line flow point and thecenter of the source stream. Measure the distance between the delivery outlet tube and the work table exit plane (d).•
Calculate the angle of deflection, Theta (θ). The angle (θ) is found as
the arctangent of the ratio expressed as (Δs)/(d) using the equation: θ
= Arctangent(Δs)/(d).• Example: if the distance between the
delivery outlet tube and the work table (d) is 4 ft. and the offset
distance (Δs) between the theoretical straight-line flow point and the
center of the source stream is 1 ft. Using the equation, we have θ =
Arctangent (1 ft./4 ft.).• θ = Arctangent 0.25.• θ = 14.036°. That means that for every 4 ft. (d) we will have no more than 1 ft. (Δs).

Acceptance: Readings
in excess of a 14-degree offset should be discussed with the customer
and either approved or corrections made until acceptable.